A 55-year-old man receiving weekly cetuximab plus irinotecan for metastatic colon cancer develops an acneiform papulopustular rash on the face and trunk, and blood tests reveal magnesium of 1.1 mg/dL with normotensive hypokalaemia. The rash and hypomagnesaemia are best explained by:
- A Irinotecan-induced cholinergic toxicity with secondary electrolyte loss
- B EGFR blockade affecting skin keratinocytes and renal tubular epithelium ✓
- C Immune complex deposition in skin and glomeruli
- D Direct cytotoxic effect of cetuximab on basal keratinocytes
Correct answer: B. EGFR blockade affecting skin keratinocytes and renal tubular epithelium
Explanation
EGFR drives proliferation and survival of epidermal basal keratinocytes, so anti-EGFR antibodies predictably cause acneiform rash whose severity paradoxically correlates with response. EGFR is also expressed in the distal convoluted tubule where it stimulates TRPM6-mediated magnesium reabsorption; blocking it causes renal magnesium wasting with hypomagnesaemia refractory to oral replacement. Irinotecan causes diarrhoea and myelosuppression, not this pattern.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.